Wound treatment systems, devices, and methods using biocompatible synthetic hydrogel compositions

Abstract

A multi-arm poly(ethylene glycol) (PEG) Succinimidyl Glutarate is mixed with a biocompatible, synthetic, nucleophilic polymer component essentially free of human or bovine albumin and other biological molecules, containing, e.g., a polypeptide moiety having a number of active surface lysines of at least twenty (20) per 5000 M/W, which can also be blended with a multi-arm poly(ethylene glycol) (PEG) Amine. The mixture forms a synthetic hydrogel composition. The synthetic hydrogel composition can be applied by topically spraying the synthetic hydrogel composition onto a targeted wound site to promote wound healing.

1 . A system for promoting wound healing comprising
 a first solution comprising a biocompatible, synthetic, electrophilic polymer component including a multi-arm poly(ethylene glycol) (PEG) Succinimidyl Glutarate,   a second solution comprising a biocompatible, synthetic, nucleophilic polymer component essentially free of human or bovine albumin and other biological molecules and including a polypeptide moiety having a number of active surface lysines of at least twenty (20) per 5000 M/W, and optionally blended with a multi-arm poly(ethylene glycol) (PEG) Amine, and   instructions for use comprising
 mixing the first and second solutions to form a synthetic hydrogel composition, and 
 applying the synthetic hydrogel composition by topically spraying the synthetic hydrogel composition onto a targeted wound site to promote wound healing. 
   
     
     
         2 . A system according to  claim 1   wherein the polypeptide moiety comprises Poly-L-Lysine hydrobromide.   
     
     
         3 . A system according to  claim 1   wherein the multi-arm poly(ethylene glycol) (PEG) Succinimidyl Glutarate has a functionality of four.   
     
     
         4 . A system according to  claim 1   wherein the optional multi-arm poly(ethylene glycol) (PEG) Amine (PEG-Amine) has a functionality of four.   
     
     
         5 . A system according to  claim 1   further including one more auxiliary component comprising salicylate-based polyanhydride-esters formulated to degrade and release salicylic acid for anti-inflammatory effect; fillers, such as glucosamine, glucosaminoglycans, and chondroitin sulfate; anti-inflamatory drugs; rapamycines and analogs, such as everohtnus and biolimus; dexamethasone; M-prednisolone; interferon γ-lb; leflunomide; mycophenolic acid; mizoribine; cyclosporine; tranilast; biorest; tacrolimus; taxius; pacitaxel; or taxol; botox; lydicane; Retin A Compound; glucosarnine; chondroitin sulfate; or Geldanamycin analogs 17-AAG or 17-DMAG; plasticizers, including cellulose and/or non-reactive PEG compounds, such as PEG-hydroxyl compounds; therapeutic agents such as stem cells, antibodies, antimicrobials, collagens, genes, DNA, and other therapeutic agents; hemostatic agents such as thrombin, chitosan, diatomaceous earth (CELOX Material), silver, and/or GELFOAM® Material; growth factors; vasoconstrictors such as Ephinephrine (which includes hydroxyl groups (—OH) and an amine group (—NH) that could be incorporated to react with PEG-SG); lydocaine; and comparable compounds.   
     
     
         6 . A system according to  claim 1   further including a dispensing unit that mixes the first and second solution and dispenses the mixture in situ through a dispensing tip, and   wherein the instructions for use direct use of the dispensing unit.   
     
     
         7 . A system according to  claim 6   wherein the dispensing unit is sized and configured as an integrated hand held device, or as an integrated hand held endoscopic device, or as an instrument system having mixing and dispensing units.   
     
     
         8 . A system according to  claim 6   wherein the dispensing tip is sized and configured as a needle, sprayer, or atomizer.   
     
     
         9 . A method for promoting wound healing comprising
 providing a first solution comprising a biocompatible, synthetic, electrophilic polymer component including a multi-arm poly(ethylene glycol) (PEG) Succinimidyl Glutarate,   providing a second solution comprising a biocompatible, synthetic, nucleophilic polymer component essentially free of human or bovine albumin and other biological molecules and including a polypeptide moiety having a number of active surface lysines of at least twenty (20) per 5000 M/W, and optionally blended with a multi-arm poly(ethylene glycol) (PEG) Amine (PEG-Amine),   mixing the first and second solutions to form a synthetic hydrogel composition, and   applying the synthetic hydrogel composition by topically spraying the synthetic hydrogel composition onto the wound site to promote wound healing.   
     
     
         10 . A system for wound healing comprising
 a first solution comprising a biocompatible, synthetic, electrophilic polymer component including a poly(ethylene glycol) (PEG) Succinimidyl Glutarate having a functionality of four and a molecular weight of about 10,000 g/mole,   a second solution comprising a biocompatible, synthetic, nucleophilic polymer component essentially free of human or bovine albumin and other biological molecules and including Poly-L-Lysine hydrobrornide having a number of active surface lysines of at least twenty (20) per 5000 M/W blended with a poly(ethylene glycol) (PEG) Amine having a functionality of four and a molecular weight of about 10,000 g/mole, wherein the weight-to-weight ratio of poly(ethylene glycol) (PEG) Amine to poly(ethylene glycol) (PEG) Succinimidyl Glutarate is selected to be about 0.7 to 1.0, and   instructions for use comprising
 mixing the first and second solutions to form a synthetic hydrogel composition, and 
 applying the synthetic hydrogel composition by topically spraying the synthetic hydrogel composition onto a targeted wound site to promote wound healing. 
   
     
     
         11 . A system according to  claim 10   wherein the first solution is essential free of a buffer material.   
     
     
         12 . A system according to  claim 10   wherein the first solution comprising poly(ethylene glycol) (PEG) Succinimidyl Glutarate dissolved in Sterile Water for Injection USP (SW1) essentially free of a buffer material.   
     
     
         13 . A system according to  claim 10   wherein the second solution comprises the Poly-L-Lysine hydrobromide and poly(ethylene glycol) (PEG) Amine dissolved in HPLC-grade water for delivery that includes a buffer material.   
     
     
         14 . A system according to  claim 10   further including a dispensing unit that mixes the first and second solution and dispenses the mixture in situ through a dispensing tip, and   wherein the instructions for use direct use of the dispensing unit.   
     
     
         15 . A system according to  claim 14   wherein the dispensing unit is sized and configured as an integrated hand held device, or as an integrated hand held endoscopic device, or as an instrument system having mixing and dispensing units.   
     
     
         16 . A system according to  claim 14   wherein the dispensing tip is sized and configured as a needle, sprayer, or atomizer.   
     
     
         17 . A system according to  claim 10   further including one more auxiliary component comprising salicylate-based polyanhydride-esters formulated to degrade and release salicylic acid for anti-inflammatory effect; fillers, such as glucosarnine, glucosaminoglycans, and chondroitin sulfate; anti-inflamatory drugs; rapamycines and analogs, such as everolimus and biolimus; dexamethasone; M-prednisolone; interferon y-1b; leflunornide; mycophenolic acid; mizoribine; cyclosporine; tranilast; biorest; tacrolimus; taxius; pacitaxel; or taxol; botox; lydicane; Retin A Compound; glucosamine; chondroitin sulfate; or Geldanamycin analogs 17-AAG or 17-DMAG; plasticizers, including cellulose and/or non-reactive PEG compounds, such as PEG-hydroxyl compounds; therapeutic agents such as stem cells, antibodies, antimicrobials, collagens, genes, DNA, and other therapeutic agents; hemostatic agents such as thrombin, chitosan, diatomaceous earth (CELOX Material), silver, and/or GELFOAMO Material; growth factors; vasoconstrictors such as Ephinephrine (which includes hydroxyl groups (—OH) and an amine group (—NH) that could be incorporated to react with PEG-SG); lydocaine; and comparable compounds.   
     
     
         18 . A method for treating burn tissue comprising
 identifying a burn tissue site,   manipulating a dispensing unit to mix a first biocompatible, synthetic, electrophilic polymer solution with a second biocompatible, synthetic, nucleophilic polymer solution to form a synthetic hydrogel composition, the first solution being essentially free of human or bovine albumin and other biological molecules and comprising poly(ethylene glycol) (PEG) Succinirnidyl Glutarate having a functionality of four and a molecular weight of about 10,000 g/mole, the second solution also being essentially free of human or bovine albumin and other biological molecules and including Poly-L-Lysine hydrobrornide having a number of active surface lysines of at least twenty (20) per 5000 114/W, optionally blended with a poly(ethylene glycol) (PEG) Amine having a functionality of four and a molecular weight of about 10,000 g/mole, and   manipulating the dispensing unit to topically spray the synthetic hydrogel composition in situ onto the burn tissue site to provide at least one of the following treatments outcomes: use of the synthetic hydrogel composition as a hemostatic agent; and/or use of the synthetic hydrogel composition as a graft fixation agent; and/or use of the synthetic hydrogel composition to reduce need for postoperative wound care; and/or use of the synthetic hydrogel composition to reduce blood loss in an individual for whom blood transfusion is unacceptable.   
     
     
         19 . A method comprising
 providing a first solution comprising a biocompatible, synthetic, electrophilic polymer component including a multi-arm poly(ethylene glycol) (PEG) Succinimidyl Glutarate,   providing a second solution comprising a biocompatible, synthetic, nucleophilic polymer component essentially free of human or bovine albumin and other biological molecules and including a target amount of a polypeptide moiety having a number of active surface lysines of at least twenty (20) per 5000 M/W, the second solution, when mixed with the first solution, forming a synthetic hydrogel composition,   titrating the target amount and molecular weight of a polypeptide moiety in the synthetic hydrogel composition to change the physical properties of the synthetic hydrogel composition in terms of elasticity; and/or stability during storage prior to use (shelf life); and/or gelation time during use; and/or degradation time after use, and   instructing mixing of the first solution with the second solution in situ to form a synthetic hydrogel composition and applying the synthetic hydrogel composition onto a targeted tissue site to promote a therapeutic benefit due to the physical properties of the synthetic hydrogel composition.   
     
     
         20 . A method according to  claim 19   wherein the polypeptide moiety is Poly-L-Lysine hydrobromide.   
     
     
         21 . A method comprising
 providing a biocompatible, synthetic, electrophilic polymer component comprising a poly(ethylene glycol) (PEG) Succinimidyl Glutarate having a functionality of four and a molecular weight of about 10,000 g/mole, providing a biocompatible, synthetic, nucleophilic polymer component comprises a poly(ethylene glycol) (PEG) Amine having a functionality of four and a molecular weight of about 10,000 g/mole that upon mixing with the electrophilic polymer component undergoes a gelation process to form a hydrogel, and   delaying onset of the gelation process by blending with the nucleophilic polymer component a Poly-L-Lysine hydrobrornide having a molecular weight of greater than about 4000 g/mole.